1. Field of the Invention
This invention is directed to novel oncokinase fusion polypeptides associated with hyperproliferative disorders and to the polynucleotides that encode for such fusion polypeptides. This invention is also directed to methods of identifying and characterizing such fusion polypeptides and polynucleotides; to methods of diagnosing disease conditions associated with such fusion polypeptides and polynucleotides; and to screening assays for identifying agents useful for treating disease conditions associated with such fusion polypeptides and polynucleotides.
2. State of the Art
An accumulation of genetic changes underlies the development and progression of hyperproliferative disorders, such as cancer, resulting in cells that differ from normal cells in their behavior, biochemistry, genetics, and microscopic appearance. Mutations in DNA that cause changes in the expression level of key proteins, or in the structures and biological activities of proteins, are thought to be at the heart of cancer. For example, cancer can be triggered when genes that play a critical role in the regulation of cell growth and survival undergo mutations that lead to their over-expression and/or activation. Such “oncogenes” are involved in the dysregulation of growth that occurs in cancers.
Kinases and phosphatases are enzymes involved in phosphorylation and dephosphorylation that help regulate many cellular activities, particularly signaling from the cell membrane to the nucleus to initiate the cell's entrance into the cell cycle and to control other functions. For example, phosphorylation is important in signal transduction mediated by receptors via extracellular biological signals such as growth factors or hormones. Many oncogenes are kinases or phosphatases, i.e. enzymes that catalyze protein phosphorylation or dephosphorylation reactions. Kinases and phosphatases may themselves be specifically regulated by phosphorylation. A kinase or phosphatase can have its activity regulated by one or more distinct kinase or phosphatases, resulting in specific signaling cascades.
Despite a long-standing need to understand and discover methods for regulating cells involved in various disease states, the complexity of signal transduction pathways has been a barrier to the development of products and processes for such regulation. Accordingly, there is a need in the art for improved methods for detecting and modulating the activity of genes involved in signal transduction and cell cycle regulation and for treating diseases associated with cancer and related disease conditions resulting from abnormal phosphorylation activity, e.g., kinase activity.